Dilated cardiomyopathy is a disease in which the contractility of the ventricular muscle is severely compromised to cause cardiac enlargement and, compared with hypertrophic cardiomyopathy, its prognosis is extremely poor. In Japan, persons surviving 5 years following the diagnosis reportedly account for about 50%. For the treatment of dilated cardiomyopathy, cardiac transplantation is preferably indicated as a radical treatment but since donations are outnumbered by cases on the waiting list, the symptomatic treatment of heart failure is a dominant treatment today. There are reported cases of improved cardiac function and prognosis following administration of an angiotensin-converting enzyme (ACE) inhibitor or a β-adrenergic blocker but the demand for efficacious therapeutic drugs and treatment is still outstanding.
Meanwhile, Matsui et al. reported that administration of a peptide derived from β1-adrenoceptor by addition of Cys to its second loop (His Trp Trp Arg Ala Glu Ser Asp Glu Ala Arg Arg Cys Tyr Asn Asp Pro Lys Cys Cys Asp Phe Val Thr Asn Arg Cys; SEQ ID NO:14) or a peptide derived from M2 muscarinic receptor by addition of Cys to its second loop (Val Arg Thr Val Glu Asp Gly Glu Cys Tyr Ile Gln Phe Phe Ser Asn Ala Ala Val Thr Phe Gly Thr Ala Ile Cys; SEQ ID NO:15) to rabbits resulted in the emergence of an antibody to each administered peptide and that the heart of rabbits that died 9 months later gave findings of dilated cardiomyopathy (Matsui S, Fu M L. Myocardial injury due to G-protein coupled receptor-autoimmunity. Jpn Heart J. 1998;39(3):261-74), thus suggesting that these antibodies act as etiologic factors in dilated cardiomyopathy. Further, Wallukat, G et al. purified an antibody against β1-adrenoceptor by using an adsorbent prepared by immobilizing the second-loop peptide of β1-adrenoceptor (His Trp Trp Arg Ala Glu Ser Asp Glu Ala Arg Arg Cys Tyr Asn Asp Pro Lys Cys Cys Asp Phe Val Thr Asn Arg; SEQ ID NO:16) on CNBr-activated Sepharose 4B (Wallukat G, Wollenberger A, Morwinski R, Pitschner H F. Anti-beta 1-adrenoceptor autoantibodies with chronotropic activity from the serum of patients with dilated cardiomyopathy: mapping of epitopes in the first and second extracellular loops. J Mol Cell Cardiol January 1995 ;27(1):397-406). However, they did not bring the serum directly into contact with the adsorbent. They first added a 40% saturated aqueous solution of ammonium sulfate to the serum to precipitate its immunoglobulin fraction (ammonium sulfate precipitation), redissolved the precipitate, dialyzed the solution, and thereafter performed a fractional purification with the adsorbent. This suggests that if the serum or the like in the state not pretreated (ammonium sulfate precipitation and dialysis) were brought into contact with the adsorbent they had synthesized, no sufficient selective adsorption should have been obtained.